The broad aim of the proposed project is to investigate the physiological control of reproduction in aged male mice. We intend to study functional changes in the brain-pituitary-testicular axis during senescence and within the framework of a new experimental paradigm. Past studies involving reproductive parameters in aging male mammals, humans or otherwise, have utilized a standard longitudinal analysis wherein comparisons were made solely on the basis of age. Such an approach confounds the reproductive-specific effects of aging with disease and with many other debilitative actions of aging which are common to all physiological systems. In contrast, we intend to compare hormonal and tissue parameters in sexually-active vs. sexually-inactive groups of aged (24 mo.) males, such groups being carefully matched for pathological condition, body weight, and performance on a treadmill. Thus by employing three-way comparisons between such groups and 6 month old males, we plan to isolate the causes of reproductive failure that are specific to the reproductive system rather than simply to determine the secondary reflections of general debilitation or disease. Previous works in the investigators's laboratories suggests that such comparisons constitute a particularly promising approach since it has enabled us to identify striking differences in LH release and in testicular testosterone secretion among aged but robust, sexually-active and -inactive male mice. We now intend to identify specific differences in (1) the responsiveness of the pituitary to GnRH and the pattern of pituitary LH, FSH, and prolactin secretion; (b) responsiveness of the testis to gonadotropin and the profile of testicular androgen and estrogen secretion; and (c) the response of the brain-pituitary-testicular axis to specific exteroceptive signals. Finally, we intend to explore the long-term effects of exercise, novelty, and sexual experience to assess the individual and combined role of these factors in the acceleration or deceleration of reproductive aging in the male.